title: ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: results from the PERTINENT study.
abstract: The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-alpha), and a biomarker of thrombosis, D-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-alpha, and D-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-alpha (27.60-25.20 pg/mL; P<0.05) and D-dimer (0.24-0.18 microg/mL; P<0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P=0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (D-dimer) and the proinflammatory cytokine TNF-alpha, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).
authors.affiliation: University of Ferrara, Salvatore Maugeri Foundation, IRCCS, Ferrara, Italy. claudio.ceconi@unife.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceconi
authors.forename: Kim M
authors.initials: KM
authors.lastname: Fox
authors.forename: William J
authors.initials: WJ
authors.lastname: Remme
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Simoons
authors.forename: Jaap W
authors.initials: JW
authors.lastname: Deckers
authors.forename: Michel
authors.initials: M
authors.lastname: Bertrand
authors.forename: Giovanni
authors.initials: G
authors.lastname: Parrinello
authors.forename: Cornelius
authors.initials: C
authors.lastname: Kluft
authors.forename: Andrew
authors.initials: A
authors.lastname: Blann
authors.forename: Dennis
authors.initials: D
authors.lastname: Cokkinos
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrari
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D003328:Coronary Thrombosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005060:Europe; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018836:Inflammation Mediators / Q000097:blood*; D053208:Kaplan-Meier Estimate; D020913:Perindopril / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; C036309:fibrin fragment D; D005340:Fibrinogen; D002097:C-Reactive Protein; D020913:Perindopril